AMK

Co-amoxiclav: Amoxicillin, clavulanic acid.

Tablet: AMK 375: Each tablet contains 250 mg of amoxicillin and 125 mg clavulanic acid.
AMK 625: Each tablet contains 500 mg of amoxicillin and 125 mg clavulanic acid.
AMK 1000: Each tablet contains 875 mg of amoxicillin and 125 mg clavulanic acid.
The amoxicillin is present as amoxicillin trihydrate and the clavulanic acid is present as clavulanate potassium.
Powder for oral suspension: AMK 156 is light pink powder with a characteristic strawberry odour, which becomes homogenous suspension when reconstituted.
AMK 156 contains 125 mg Amoxicillin (Amoxicillin Trihydrate) and 31.25 mg Clavulanic Acid (Potassium Clavulanate) per 5 ml.
AMK 457 is light pink powder with a characteristic strawberry odour, which becomes homogenous suspension when reconstituted.
AMK 457 contains 400 mg Amoxicillin (Amoxicillin Trihydrate) and 57 mg Clavulanic Acid (Potassium Clavulanate) per 5 ml.

Tablet: Pharmacology: AMK is a combination of amoxicillin and clavulanic acid. Amoxicillin, a penicillin antibiotic with a broad spectrum of bactericidal activity, and clavulanic acid, an irreversible beta-lactamase inhibitor. With enzymes it produces stable nonactive complexes and protects amoxicillin from degradation.
Antibacterial Spectrum: Gram-positive aerobes (S. pneumonia, S. pyogenes, S. viridans, S. aureus); Gram-negative aerobes (H. influenzae, Moraxella catarrhalis, E. coli, Klebsiella spp., N. gonorrhoeae); Anaerobes (Peptostreptococcus spp.).
Pharmacokinetics: Amoxicillin and Clavulanic acid are both well absorbed after oral administration and are stable in the presence of gastric acid. Food has no effect on the degree of absorption.
Peak serum concentrations are achieved approximately 1-2.5 hours after ingestion. Amoxicillin and Clavulanate potassium combination is eliminated primarily unchanged through the renal route. In patients with impaired renal function excretion of the drug from the body is delayed.
Powder for oral suspension: Pharmacology: Pharmacokinetics: Absorption: Amoxicillin trihydrate and clavulanate potassium are both generally stable in the presence of acidic gastric secretions and are well absorbed following oral administration of amoxicillin and clavulanate potassium. Peak serum concentrations of amoxicillin and of clavulanic acid are generally attained within 1-2.5 hours following oral administration of a single dose of conventional preparations of amoxicillin and clavulanate potassium in fasting adults.
Distribution: Following administration of amoxicillin and clavulanate potassium, amoxicillin and clavulanic acid are both distributed into the lungs, pleural fluid, and peritoneal fluid. Low concentrations of each drug are attained in sputum and saliva. Only minimal concentrations of amoxicillin or clavulanic acid are attained in CSF following oral administration of amoxicillin and clavulanate potassium in patients with uninflamed meninges; higher concentrations may be attained when meninges are inflamed. Amoxicillin is 17-20% bound to serum proteins. In vitro or in vivo following oral administration, clavulanic acid is reportedly 22-30% bound to serum proteins at concentration of 1-100 μg/ml.
Amoxicillin and clavulanic acid readily cross the placenta. Amoxicillin and clavulanic acid are distributed into milk in low concentrations.
Elimination: Following oral administration of a single oral dose of amoxicillin and clavulanate potassium in adults with normal renal function, amoxicillin has an elimination half-life of 1-1.3 hours and clavulanic acid has a distribution half-life of 0.28 hours and an elimination half-life of 0.78-1.2 hours.
The metabolic fate of clavulanate potassium has not been fully elucidated; however, the drug appears to be extensively metabolized. In rats and dogs, the major metabolite of clavulanic acid is 1-amino-4-hydroxybutan-2-one; this metabolite has also been found in human urine following administration of clavulanic acid. Clavulanic acid is excreted in urine principally by glomerular filtration.
Following oral administration of a single oral dose of amoxicillin and clavulanate potassium in adults with normal renal function, approximately 50-73 and 25-45% of the amoxicillin and clavulanic acid doses, respectively, are unchanged in urine within 6-8 hours.
Serum concentrations of amoxicillin and of clavulanic acid are higher and the serum half-lives prolonged in patients with renal impairment.
Pharmacodynamics: Amoxicillin and clavulanate potassium usually is bactericidal in action. Concurrent administration of clavulanic acid does not alter the mechanism of action of amoxicillin. However, because clavulanic acid has a high affinity for and binds to certain β-lactamase that generally inactivates amoxicillin by hydrolyzing its β-lactam ring, concurrent administration of the drug with amoxicillin results in synergistic bactericidal effect which expands the spectrum of activity of amoxicillin against many strains of β-lactamase-producing bacteria that are resistant to amoxicillin alone.
Clavulanic acid generally acts as an irreversible, competitive inhibitor of β-lactamase. The mechanism by which clavulanic acid binds to and inhibits β-lactamase varies depending on the specific β-lactamase involved. Because clavulanic acid is structurally similar to penicillins and cephalosporins, it initially acts as a competitive inhibitor and binds to the active site on the β-lactamase.

Tablet: Upper respiratory tract infections eg. sinusitis, otitis media; Lower respiratory tract infections eg. acute exacerbation of chronic bronchitis, pneumonia; Urinary tract infections; Skin and soft tissue infections; Dental infections.
Powder for oral suspension: Used orally in adults and children for the treatment of abscess, cellulites and impetigo caused by susceptible penicillinase-producing and nonpenicillinase-producing Staphylococcus aureus and S. epidermidis, Streptococcus pyogenes (group A β-hemolytic streptococci) or Corynebacterium.
Used in adults or children for the treatment of otitis media or upper and lower respiratory tract infections such as bronchopneumonia, sinusitis, and acute exacerbations of chronic bronchitis caused by susceptible H. influenzae.
Chancroid.
Infections caused by β-lactamase-producing M. catarrhalis.
Used orally with success for the treatment of uncomplicated gonorrhea caused by penicillinase producing strains of N. gonorrhoeae (PPNG) or nonpenicillinase-producing strains of the organism.
Urinary Tract Infections: Used orally in adults or children for the treatment of uncomplicated or complicated urinary tract infections (UTIs) caused by susceptible organisms including E. coli, Klebsiella, Enterobacter, or P. mirabilis.
Used orally with some success in a limited number of patients for the treatment of anaerobic and mixed aerobic-anaerobic bacterial infections including intra-abdominal and gynecologic infections such as endometritis, salpingitis, pelvic cellulitis, and acute pelvic inflammatory disease.

Tablet: In Children: The exact doses are based on body weight. Depending upon severity of infection, the daily dose in children under 40 kg body weight is 20-40 mg/kg body weight (based on the amoxicillin component) in divided dose three times daily.
Adults and children over 12 years: Mild-Moderate infections: AMK 375 mg tablet three times a day.
Severe infections: AMK 1 g tablet two times a day.
In patients with severe renal insufficiency (creatinine clearance 10 to 30 ml/min) the dose should be adequately adjusted or the dosing interval prolonged, in anuria to 48 hours or more (creatinine clearance less than 5 ml/min).
Powder for oral suspension: AMK 156/457 for oral suspension should be reconstituted at the time of dispensing by adding the water to the mark on the bottle. After tapping the bottle to thoroughly loosen the powder for oral suspension, the water should be added to the powder in 2 portions and the suspension agitated well after each addition. The suspension should be agitated well just prior to administration of each dose.
Usual dose range: Dosage of amoxicillin and clavulanate potassium generally is expressed in terms of the amoxicillin content of the fixed combination.
Infants <3 months: Oral: 30 mg/kg/day divided every 12 hours using 125 mg/5 ml of amoxicillin.
Children ≥3 months and <40 kg: Oral: 20-90 mg/kg/day divided every 8-12 hours.
Children ≥40 kg and Adults: Oral: 250-500 mg every 8 hours or 875 mg every 12 hours.

Tablet: Intoxication with AMK is unlikely to occur. However, ingestion of a larger number of tablets may produce agitation, insomnia, dizziness, in some cases seizures. Treatment is symptomatic.
Amoxicillin can be removed by dialysis.

Tablet: Hypersensitivity to amoxicillin, clavulanic acid and penicillin group of antibiotics.
Powder for oral suspension: Hypersensitivity to amoxicillin, clavulanic acid and penicillin, or any component of the formulation; history of cholestatic jaundice or hepatic dysfunction with amoxicillin/clavulanate potassium therapy.

Tablet: Should be used with caution in patients with a history of allergic reactions. In patients with severely impaired liver or renal function the dose should be adequately reduced or the dosing interval prolonged.
Powder for oral suspension: Hypersensitivity reactions, including anaphylaxis.
Prolonged use may result in fungal or bacterial superinfection.
In patients with renal impairment, doses and/or frequency of administration should be modified in response to the degree of renal impairment.
High percentage of patients with infectious mononucleosis have developed rash during therapy, ampicillin-class antibiotics not recommended in these patients.
Incidence of diarrhea of amoxicillin/clavulanic acid is higher than with amoxicillin alone. Due to differing content of clavulanic acid, not all formulations are interchangeable.
Low incidence of cross-allergy with cephalosporins exists.

Tablet: There is no evidence of teratogenic effect to the fetus. AMK can be used during pregnancy if clearly indicated. Both amoxicillin and clavulanic acid have been shown to be excreted in minor quantities in breast milk. It should be used with caution in nursing women.
Powder for oral suspension: Safe use of amoxicillin and clavulanate potassium during pregnancy has not been definitely established. However, oral amoxicillin and clavulanate potassium has been used in a limited number of pregnant women for the treatment of urinary infections or acute pelvic inflammatory disease without evidence of adverse effects to the fetus. There are no adequate or controlled studies using amoxicillin and clavulanate potassium in pregnant women, and the drug should be used during pregnancy only when clearly needed.
Amoxicillin and clavulanic acid are distributed into milk, amoxicillin and clavulanate potassium should be used with caution in nursing women.

Tablet: Adverse reactions are usually of a mild nature. The most frequently reported are digestive disorders (nausea, vomiting, diarrhea, abdominal discomfort, anorexia, flatulence and dyspepsia). These reactions can be minimized if the drug is taken with meals. Skin reactions may occur. A rise in hepatic enzymes may rarely occur. Cholestatic jaundice, hepatitis, interstitial nephritis. Leukopenia, thrombocytopenia, eosinophilia may occur.
Powder for oral suspension: Dermatologic: Diaper rash, skin rash, urticaria.
Gastrointestinal: Abdominal discomfort, diarrhea, loose stools, nausea, vomiting.
Genitourinary: Vaginitis, vaginal mycosis.
Miscellaneous: Moniliasis.
Rare but important or life-threatening: Alkaline phosphatase increased, Cholestatic jaundice, flatulence, headache, hepatic dysfunction, hepatitis, liver function tests increased, prothrombin time increased, thrombocytosis, vasculitis (hypersensitivity).

Tablet: Probenecid may increase amoxicillin levels. Increased effect of anticoagulants with amoxicillin. Efficacy of oral contraceptives may be reduced when taken with AMK.
Powder for oral suspension: Probenecid: Oral probenecid administered shortly before or concomitantly with amoxicillin and clavulanate potassium slows the rate of renal tubular secretion of amoxicillin and produces higher and prolonged serum concentrations of amoxicillin.
Allopurinol: Increased incidence of rash reportedly occurs in patients with hyperuricemia who are receiving allopurinol and concomitant amoxicillin compared with those receiving amoxicillin or allopurinol alone.
Disulfiram: There is no evidence to date that concomitant use of the drugs would result in a disulfiram-like reaction, and the need for precaution when concomitant use of the drugs is considered has been questioned.

Tablet: Store the drug at a temperature below 25°C, protected from humidity.
Powder for oral suspension: Store the powder below 25°C.
Store the reconstituted suspension in refrigerator and use it within 7 days.

Penicillins

J01CR02 - amoxicillin and beta-lactamase inhibitor ; Belongs to the class of penicillin combinations, including beta-lactamase inhibitors. Used in the systemic treatment of infections.

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